Ranitidine is a best-selling drug used to reduce high stomach acid. Through its lowering effect on stomach acid, it is widely used in the treatment of conditions such as gastroesophageal reflux, ulcers in the stomach and bowel, erosive esophagitis, and Zollinger-Ellison syndrome. Read on to learn more about this medication, its health benefits, and main adverse effects.
Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.
What Is Ranitidine (Zantac)?
Ranitidine is a drug that decreases stomach acid production and is therefore employed in the treatment and prevention of disorders related to excessive stomach acid [1].
Developed in 1977, ranitidine was first introduced into the market in 1981 and quickly became the best-selling drug worldwide [2].
The main brand names for ranitidine are Zantac® and Taladine®.
Ranitidine is a histamine blocker. By binding to the H2-receptors on the stomach acid-producing cells, it prevents their activation by histamine [3].
Prescription ranitidine comes as tablets (oral and effervescent), capsules, and syrup. This medication is mainly used to treat [1]:
- Ulcers of the stomach and bowel
- Esophagus inflammation
- Gastroesophageal reflux disease (GERD)
- Zollinger-Ellison syndrome
It is also sold over-the-counter (OTC) as 75 mg and 150 mg tablets to prevent symptoms of excessive acid in the stomach such as [4, 5]:
- Heartburn
- Acid indigestion
Mechanism of Action
Histamine is a compound that is produced by white blood cells (mast cells and basophils), platelets, immune cells (lymphocytes), brain cells, and secreting cells in stomach glands (enterochromaffin cells) [6].
In the stomach, histamine is produced by enterochromaffin cells and activates those that produce acid (parietal cells) by binding to the H2-receptors on their surface [7].
Ranitidine and other H2-receptor blockers were designed by using histamine as a starting point and modifying its chemical structure [8].
These chemicals compete with histamine for binding to the H2-receptor. The reversible interaction between a blocker and the receptor prevents the binding of histamine, and thus the activation of acid production [9].
Uses of Ranitidine
Over-the-counter ranitidine is approved to prevent and relieve heartburn associated with acid ingestion and sour stomach. Prescription ranitidine is mainly approved for the treatment and prevention of ulcers of the stomach and intestines and gastroesophageal reflux disease.
Follow your doctor’s instructions carefully. Take ranitidine as recommended and do not change its dose and frequency or stop taking it without your doctor’s approval. Your healthcare provider may recommend you combine ranitidine with other medications (such as antacids and PPIs). Talk to your doctor if your condition doesn’t improve or if it worsens.
Effective for:
1) Gastroesophageal Reflux Disease (GERD)
Gastroesophageal reflux disease (GERD) is the abnormal entry of stomach acid into the esophagus. The main symptoms of this disease, which affects 20% of the US adult population at least once a week, are heartburn and regurgitation [10].
GERD normally occurs when the muscle closing the stomach opening cannot counteract the internal pressure of this organ [11, 12].
The main factors triggering GERD are [13, 14]:
Ranitidine reduced GERD symptoms such as heartburn and esophagitis in several trials [15, 16].
Ranitidine outperformed an antacid (calcium carbonate) in relieving heartburn in a clinical trial on over 150 people with GERD [17].
Low doses of ranitidine decreased stomach acid for 9 hours in a small trial on 24 healthy people [18].
High doses of ranitidine showed better GERD relieving capacity in 2 small trials on 38 people [19, 20].
However, a small trial on 18 people with GERD showed the development of tolerance to the medication after long-term treatment with ranitidine, resulting in a reduced efficiency [21].
In a small trial on 29 children, low doses of ranitidine reduced stomach acid [4].
In a small trial on 18 pregnant women, ranitidine twice daily relieved GERD symptoms more efficiently than the same dose once daily [22].
However, PPIs generally outperform ranitidine in the treatment of this disease.
Several studies showed a better efficiency of omeprazole compared to ranitidine in the management of GERD symptoms [23, 24, 25, 26].
In several studies, lansoprazole treated GERD more efficiently than ranitidine [27, 28].
Pantoprazole also relieved GERD symptoms more efficiently than ranitidine [29, 30].
Both ranitidine and omeprazole were equally efficient in treating GERD symptoms in a clinical trial on 76 children [31].
2) Heartburn
Heartburn is a burning and painful sensation in the chest and upper stomach that is normally due to the entry of stomach acid into the esophagus, and is the main symptom of gastroesophageal reflux disease (GERD) [32].
Heartburn is generally well controlled with antacids. While H2-receptor blockers and PPIs prevent the formation of acid in the stomach, antacids neutralize it after its production [33].
In a clinical trial on almost 100 people with self-perceived heartburn taking either an antacid (Maalox) or ranitidine, the antacid was faster in relieving heartburn symptoms [34].
In a small trial on 26 people with frequent meal-induced heartburn, ranitidine was faster at reducing stomach acidity, while the effect of the antacid (calcium carbonate) was faster in the esophagus [35].
In a longer-term trial on over 150 people suffering from heartburn frequently, ranitidine was more effective than antacid (calcium carbonate) in relieving heartburn, curing erosive esophagitis, reducing pain, and improving life quality [17].
In several trials, ranitidine efficiently relieved heartburn symptoms within 30 to 60 minutes and lasted up to 12 hours [36, 37, 14, 38].
Ranitidine reduced heartburn symptoms and esophagus sensitivity to acid in 2 independent trials [39, 40].
However, doubling the dose to 300 mg did not improve the recovery rate in the first trial [39].
3) Erosive Esophagitis
A small proportion of people with gastroesophageal reflux disease (GERD) develop erosive esophagitis, in which the lining of the esophagus is inflamed and worn away [41].
Those whose esophagus is in contact with stomach acid for extended periods have the highest risk of developing erosive esophagitis [42].
High doses of ranitidine were effective in treating erosive esophagitis in several studies [43, 44, 45].
In a small trial on 7 people with erosive esophagitis, low doses of ranitidine decreased the exposure of the esophagus to acid, but failed to reduce it to normal values [46].
In several trials, omeprazole treated erosive esophagitis more effectively than the combination of ranitidine and metoclopramide [47, 48].
Similarly, rabeprazole and lansoprazole were more effective than ranitidine against erosive esophagitis in multiple studies [49, 50].
In a trial on almost 400 people with erosive esophagitis being treated with proton pump inhibitors (PPIs), adding ranitidine improved heartburn symptoms in the short term, but patients eventually developed tolerance [51].
4) Zollinger-Ellison Syndrome
Zollinger-Ellison syndrome is the presence of a tumor, normally in the pancreas, bowel, or nodes on the stomach, which produces a hormone (gastrin) that stimulates the increased release of stomach acids [52].
The symptoms are caused by the excess of acid and include [53]:
- Ulcers in the bowel
- Gastroesophageal reflux
- Diarrhea
- Nausea
- Loss of appetite
- Bleeding
Excessive acid production can be treated with H2-receptor blockers. Due to its low side effects and limited interactions with other drugs, ranitidine is often the treatment of choice [54].
High doses of ranitidine have been successfully used in the management of this syndrome [55, 56, 57, 58].
Low doses of omeprazole have been used as an alternative to H2-receptor blockers [59, 60, 61].
Ranitidine has also been effectively used in managing Zollinger-Ellison syndrome in pregnant women [62].
5) NSAID-Induced Complications
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to treat inflammatory conditions and reduce pain. Their long-term use is associated with increased risk of developing ulcers in the stomach and bowel [63, 64].
In several clinical trials, ranitidine prevented and healed NSAID-induced ulcers [65, 66, 67, 68, 69].
In 2 studies in rats, ranitidine reduced stomach ulceration and bleeding caused by NSAIDs [70, 71].
Given their stronger action, PPIs have been included in trials comparing their efficiency to that of ranitidine against NSAID-induced ulcers.
In a clinical trial of over 500 people on NSAID with ulcers in the stomach or bowel, omeprazole was more effective than ranitidine in healing and preventing ulcers [72].
In 2 studies, the healing rate of NSAID-induced stomach ulcers was higher in people taking lansoprazole than in those taking ranitidine [73, 74].
The efficiency of esomeprazole in healing NSAID-induced stomach ulcers was higher in people taking esomeprazole than in those taking ranitidine in one trial on over 400 people, but comparable in a similar one [75, 76].
6) Ulcers
Stress-Induced Ulcers
Critically ill patients, such as those in intensive care units, are more prone to stomach ulcers [77].
In some cases, the ulcers can cause severe bleeding and lead to complications (such as anemia, shock, or chest pain) and death [78].
Because stress-induced ulcers are uncommon at low acid levels in the stomach, H2-receptor inhibitors are very popular for prevention of ulcers [79].
In a small trial on 37 people in intensive care units, ranitidine efficiently reduced stomach acidity, thus preventing the appearance of stress-induced ulcers [80].
In another trial on 48 newborn babies in the neonatal intensive care unit, short-term treatment with ranitidine prevented the appearance of stomach ulcers [81].
However, in a trial on almost 100 people in intensive care units with normal liver and kidney function subjected to long-term mechanical ventilation, ranitidine did not decrease the incidence rate of stress-induced ulcers [82].
In a meta-analysis of 3 studies, omeprazole was as effective as ranitidine in the prevention of stress-induced ulcers [83].
In contrast, sucralfate (a drug that binds to ulcers and creates a protective barrier against stomach acids) was at least as effective as ranitidine in preventing the appearance of stress-induced ulcers and reduced the risk of pneumonia in 2 trials [84, 85].
Stomach and Intestinal Ulcers
Ulcers are breaks in the lining of the stomach or first part of the small intestine.
The main symptoms are [86]:
- Stomach pain
- Loss of appetite
- Regurgitation
- Nausea
- Vomiting of blood
- Weight loss
Ranitidine has been successfully used to treat ulcers in the stomach and bowel in several trials [87, 88, 89, 90].
A single bedtime dose of 300 mg ranitidine was as safe and effective in healing ulcers as the standard dose of 150 mg twice per day in several studies [91, 92, 93].
In several trials on people with healed stomach and bowel ulcers, ranitidine was an effective maintenance therapy to prevent relapse [94, 95, 96, 97].
In several studies, omeprazole was more effective than a standard dose of ranitidine in the treatment of stomach and bowel ulcers [98, 99, 100, 101].
Helicobacter Pylori-Induced Ulcers and Complications
Helicobacter pylori is a bacteria that infects the digestive system. Although most infected individuals do not show symptoms of disease, infection with this bacteria is responsible for most ulcer cases diagnosed [102].
Ranitidine bismuth citrate, previously sold under the brand name Titrec® and now available as a generic drug, is an effective treatment against H. pylori-induced ulcers. This drug combines the acid-decreasing action of ranitidine and the antimicrobial and mucosal-protective roles of bismuth [103].
The combination of ranitidine bismuth citrate with the antibiotic clarithromycin was more effective in healing ulcers and eradicating H. pylori than ranitidine bismuth citrate alone in several studies [104, 105, 106, 107].
A clinical trial on over 200 people showed that amoxicillin could be used as an alternative to clarithromycin in those intolerant or resistant to this antibiotic [108].
The healing effect is enhanced by designing a triple therapy combining both amoxicillin and clarithromycin, as seen in 2 trials on over 200 people [109, 110].
In a trial on over 500 people with duodenal ulcer and H. pylori infection, a dual therapy with clarithromycin and omeprazole was as effective as one with this antibiotic and ranitidine bismuth citrate [111].
Both ranitidine bismuth citrate and omeprazole were equally effective in triple therapies with amoxicillin and clarithromycin in several studies [112, 113, 111, 114].
However, ranitidine bismuth citrate in triple therapy with amoxicillin and clarithromycin eradicated H. pylori more efficiently than all PPIs except rabeprazole in a trial on almost 400 people [115].
7) Prevention of Acid Aspiration During Surgery
Acid aspiration is the inhalation of regurgitated stomach acids into the lungs. This complication may occur during surgical procedures [116].
Acid aspiration is particularly harmful to patients when the stomach is full and the acid level is high [117].
In a trial on almost 300 people about to undergo surgery, ranitidine twice per day reduced both stomach content volume and acid levels [118].
In another trial on 75 children, intake of water plus ranitidine prior to surgery reduced their risk of acid aspiration and improved their behavior [119].
The combination of ranitidine with pirenzepine reduced both stomach content volume and acidity in a clinical trial on over 100 children [120].
PPIs like omeprazole and pantoprazole were as effective as ranitidine against acid aspiration in several trials [121, 122, 123].
8) Inhibition of Allergic Response
Because they prevent histamine activity, H2-receptor blockers like ranitidine may reduce the allergic response to some agents [124].
Ranitidine relieved the symptoms of skin allergic reactions in several trials [125, 126, 127, 128].
In 2 clinical trials of people with skin allergic conditions, ranitidine enhanced the healing effects of the therapy with H1-receptor blockers [129, 130].
In 2 additional studies, ranitidine was effective against some symptoms of allergic nose inflammation [131, 132].
Henoch-Schönlein vasculitis is the inflammation of blood vessels caused by the allergic reaction to infections or drugs.
Its main symptoms include [133]:
- Red- or purple-colored spots on the skin
- Arthritis
- Stomach pain
- Stomach and bowel bleeding
- Blood in the urine
In a small trial on 12 people with Henoch-Schönlein vasculitis, treatment with ranitidine reduced the duration and severity of stomach pain and bleeding [134].
9) Gut Bleeding
Gut bleeding is a condition in which blood vessels of the stomach, esophagus, or bowel are broken. It can be life-threatening if it affects large vessels [135].
Its most common causes are:
- Ulcers in the stomach and bowel [136]
- Mallory-Weiss tear [137]
- Stress-induced stomach inflammation [138]
- Dieulafoy lesions [139]
- Dilated veins in the stomach [140]
Ranitidine effectively controlled acute gut bleeding in several trials [141, 142, 143].
In 2 trials, ranitidine reduced gut bleeding by reducing the acid level of the stomach [144, 145].
However, omeprazole was more effective than ranitidine in treating upper gut bleeding in a trial on almost 100 people [146].
In a multi-center trial on 1200 people requiring mechanical ventilation, ranitidine reduced gut bleeding more efficiently than sucralfate [147].
However, the evidence for the effects of ranitidine and sucralfate in preventing gut bleeding in critically ill patients was found insufficient in multiple studies [148, 149, 150].
Insufficient Evidence for:
10) Colorectal Cancer Therapy
H2-receptor blockers may prevent 3 cancer-promoting effects of histamine:
- Increased activity of immune-suppressing cells [151]
- Prevention of tumor recognition by immune cells [152]
- Promotion of cancer cell growth [153]
In a trial on over 500 people with cancer in the large bowel who underwent tumor removal, treatment with ranitidine for 5 years improved survival in those who did not receive blood transfusions during the surgical procedure [154].
In blood from 25 people with cancer in the large bowel, the combination of ranitidine with low doses of the cytokine IL-2 increased the activity of natural killer cells [155].
In cell trials, ranitidine reduced the growth and increased the death of colorectal cancer cells [156].
11) Bowel Inflammation
Inflammatory bowel disease (IBD) is the long-term inflammation of the intestines, suspected to be due to a malfunction of the immune system.
The two main types of IBD are [157]:
- Ulcerative colitis
- Crohn’s disease
The main symptoms common to both types of IBD are:
An increased production of both histamine and its by-products are observed in patients with IBD [158, 159, 160, 161].
Forms and Dosage
Oral ranitidine is mostly sold in the following forms [162, 163]:
- Tablets: 75, 150, and 300 mg
- Capsules: 150 and 300 mg
- Syrup: 75 mg/5 ml
For people who cannot take ranitidine by mouth, flasks of ranitidine-HCl (25 mg/ml) are available for injection [164].
The most common over-the-counter doses to treat and prevent heartburn and acid indigestion are 75 and 150 mg per use per day [5].
Doubling the standard dose to 300 mg of ranitidine twice per day does not improve its efficiency in treating gastroesophageal reflux symptoms [39].
In people suffering from stomach and bowel ulcers, one single dose of 300 mg ranitidine daily is as effective as two doses of 150 mg per day [165].
In the treatment of erosive esophagitis, the recommended doses are ranitidine 300 mg twice daily or 150 mg per day 4 times daily [45].
Zollinger-Ellison syndrome can be treated with very high doses (up to 2.1 g ranitidine per day) [166].
Ranitidine is very safe and doses up to 6 g per day are generally well tolerated [167].
However, side effects have been reported. For more, check out this post.
The incidence of overdose cases has been highest among children under 6 months and patients with kidney failure. The main symptoms of overdose include [168, 169]:
- Sleepiness
- Confusion
- Disorientation
- Nausea
- Dizziness
Limitations and Caveats
Studies on the role of ranitidine in healing and preventing stress-induced ulcers show contradicting results [80, 82].
The evidence for the effects of ranitidine on skin allergic reactions is based on a few studies of a relatively small size with a certain risk of bias [170].
The evidence for the effects of ranitidine and sucralfate in preventing gut bleeding in critically ill patients was found insufficient in several studies [148, 149, 150].
The healing effect of ranitidine on intestinal bleeding is mostly speculated based on the role of histamine and its by-products in these diseases [158, 159, 160, 161].
More evidence is needed to evaluate the efficiency of ranitidine in colorectal cancer therapy [154].
Further Reading
Takeaway
Ranitidine, sold under the brand name Zantac®, is an H2 histamine receptor blocker that is prescribed to treat disorders caused by too much stomach acid production, such as gastric ulcers, GERD, heartburn, and erosive esophagitis.
It is also sometimes used to prevent acid aspiration during surgery and to help with allergic reactions and gut bleeding. Some early clinical evidence suggests that it may have a use in colorectal cancer therapy and to reduce bowel inflammation, but additional research is required.
Ranitidine is generally given in doses of between 75 and 300 mg per day, though higher doses are occasionally used. Make sure to follow your doctor’s instructions precisely if you are prescribed ranitidine.
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